ArticleScientific reports2015
Translocation of Non-Canonical Polypeptides into Cells Using Protective Antigen.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Anthrax Toxin: A Pioneer of Targeted Protein Toxins.Toxins · 2025Review
- Review
- AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy.International journal of molecular sciences · 2023Review
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Challenges and approaches to studying pore-forming proteins.Biochemical Society transactions · 2021Review
- Thermodynamic Stability Is a Strong Predictor for the Delivery of DARPins to the Cytosol via Anthrax Toxin.Pharmaceutics · 2021Article
- Harnessing the Membrane Translocation Properties of AB Toxins for Therapeutic Applications.Toxins · 2021Review
- Anthrax Protective Antigen Retargeted with Single-Chain Variable Fragments Delivers Enzymes to Pancreatic Cancer Cells.Chembiochem : a European journal of chemical biology · 2020Article
- Targeting Cancer Gene Dependencies with Anthrax-Mediated Delivery of Peptide Nucleic Acids.ACS chemical biology · 2020Article
- Article
- Fluorescence Correlation Spectroscopy Reveals Efficient Cytosolic Delivery of Protein Cargo by Cell-Permeant Miniature Proteins.ACS central science · 2018Article
- Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts.Chemical reviews · 2018Review
- Tumor Targeting and Drug Delivery by Anthrax Toxin.Toxins · 2016Review
- Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.Scientific reports · 2016Article
- The Ins and Outs of Anthrax Toxin.Toxins · 2016Review
- A d-Amino Acid at the N-Terminus of a Protein Abrogates Its Degradation by the N-End Rule Pathway.ACS central science · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A variety of pathogenic bacteria infect host eukaryotic cells using protein toxins, which enter the cytosol and exert their cytotoxic effects. Anthrax lethal toxin, for example, utilizes the membrane-spanning translocase, protective antigen (PA) pore, to deliver the protein toxin lethal factor (LF) from the endosome into the cytosol of cells. Previous work has investigated the delivery of natural peptides and enzymatic domains appended to the C-terminus of the PA-binding domain of lethal factor (LFN) into the cytosol via PA pore. Here, we move beyond natural amino acids and systematically investigate the translocation of polypeptide cargo containing non-canonical amino acids and functionalities through PA pore. Our results indicate translocation is not perturbed with alterations to the peptide backbone or side-chain. Moreover, despite their structural complexity, we found that the small molecule drugs, doxorubicin and monomethyl auristatin F (MMAF) translocated efficiently through PA pore. However, we found cyclic peptides and the small molecule drug docetaxel abrogated translocation due to their large size and structural rigidity. For cargos that reached the cytosol, we demonstrated that each remained intact after translocation. These studies show PA is capable of translocating non-canonical cargo provided it is in a conformational state conducive for passage through the narrow pore.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.